A long-term goal of this research is to understand the molecular mechanisms by which Sinorhizobium meliloti invades the nodules that it elicits on its plant hosts and establishes a productive symbiosis. Another long-term goal is to use knowledge gained from this research to increase our understanding of other bacterial-host interactions, particularly those involving chronic infections of mammals by bacterial pathogens. We have already shown that the synthesis of any of three different S. meliloti extracellular polysaccharides (succinoglycan, EPS II, and K antigen) in a symbiotically active low molecular weight form is required for invasion through infection threads. We will further characterize the quorum sensing regulation of these exopolysaccharides, examine the regulatory role of ExoS-ChvI, and further analyze their biosynthetic mechanisms. We will carry out studies of how the symbiotically active forms of the exopolysaccharide interact with the plant and will test how alteration of the chemical structure, non-carbohydrate modification, and molecular weight distribution of exopolysaccharide influence the architecture of biofilms. We have shown that S. meliloti, a plant symbiont, and Brucella abortus, an animal pathogen, both require the function of the bacA gene for the chronic intracellular infections they cause in their respective hosts. The proposed research will determine the molecular basis of bacA function, test the importance of bacA in other chronic host-pathogen interactions, and further explore possible commonalities between S. meliloti symbiosis and B. abortus pathogenesis. By taking advantage of the recent sequencing of the S. meliloti genome, we have identified 30 genes previously unrecognized as being important for symbiosis and will further study the roles of the most interesting of these. Our work demonstrating the importance of BacA protein in Brucella chronic infections has identified it as a possible target for new classes of drugs active against chronic infections. There is no human vaccine for Brucella, a potential bioterrorism threat, and B. abortus bacA mutants are potential vaccines. Our work will continue to offer insights into how specific low molecular weight oligosaccharides can serve as signals to eukaryotic hosts.